Drotrecogin alfa in patients with severe sepsis: experience from a tertiary care center in North India

Introduction

Drotrecogin alfa (DA) remains the only approved drug for the specific treatment of severe sepsis. Although it has been in wide clinical usage, there are no data on its use in Indian patients.

Methods

Fifty-seven patients with severe sepsis (age 51 ± 15 years, range 20–77 years, male:female 32:25) admitted to the ICU were included. All patients had three or more signs of systemic inflammation with at least two major organ dysfunctions or the presence of ARDS. Demographic, clinical and laboratory profiles at baseline, and during the hospital stay, development of complications, duration of hospital/ICU stay and hospital survival were recorded. All management decisions including initiation of DA (24 μ/kg/hour), duration of treatment as well as its discontinuation were the prerogative of the ICU team.

Results

The majority of patients had a confirmed infection (n = 36, 63.2%), with the commonest site of focus being the lung (n = 25, 43.9%) followed by the abdomen (n = 13, 22.8%). A significant number of patients had at least three major organ dysfunctions (n = 37, 64.9%). A large number of patients had an APACHE II score in the range 25–29 (n = 22, 38.6%). Whereas 44 patients (77.2%) were on some kind of vasopressor support, 51 needed ventilatory support (89.5%). A total of 20 patients (35.1%) survived to hospital discharge. Patients received DA for a mean duration of 74.8 ± 26.2 hours (range 25–96 hours) and only 32 patients could complete treatment (56.1%). The outcome was significantly better in patients who could complete therapy (53.1% vs 13.6%, P = 0.001). Major bleeding necessitating discontinuation was seen in four patients (7%) whereas the other 21 patients (36.9%) died before completing 96 hours of therapy. DA was initiated within 48 hours of development of organ dysfunction in the majority of patients (n = 31, 54.4%), and a trend towards better outcome in patients with early treatment was noted although the difference did not reach statistical significance (mortality rate 58% for early treatment vs 73.1% for delayed treatment, P = not significant).

Conclusion

Mortality of patients with severe sepsis remains high despite the introduction of DA. Early institution may be associated with better outcomes. Patients receiving a complete course of treatment have better survival.